School of Psychology and Psychiatry, Monash University, Melbourne, VIC, Australia.
Neuropsychopharmacology. 2013 Jul;38(8):1598-606. doi: 10.1038/npp.2013.59. Epub 2013 Feb 28.
The adverse effects of cannabis use on executive functions are still controversial, fostering the need for novel biomarkers able to unveil individual differences in the cognitive impact of cannabis consumption. Two common genetic polymorphisms have been linked to the neuroadaptive impact of Δ9-tetrahydrocannabinol (THC) exposure and to executive functions in animals: the catechol-O-methyltransferase (COMT) gene val158met polymorphism and the SLC6A4 gene 5-HTTLPR polymorphism. We aimed to test if these polymorphisms moderate the harmful effects of cannabis use on executive function in young cannabis users. We recruited 144 participants: 86 cannabis users and 58 non-drug user controls. Both groups were genotyped and matched for genetic makeup, sex, age, education, and IQ. We used a computerized neuropsychological battery to assess different aspects of executive functions: sustained attention (CANTAB Rapid Visual Information Processing Test, RVIP), working memory (N-back), monitoring/shifting (CANTAB ID/ED set shifting), planning (CANTAB Stockings of Cambridge, SOC), and decision-making (Iowa Gambling Task, IGT). We used general linear model-based analyses to test performance differences between cannabis users and controls as a function of genotypes. We found that: (i) daily cannabis use is not associated with executive function deficits; and (ii) COMT val158met and 5-HTTLPR polymorphisms moderate the link between cannabis use and executive performance. Cannabis users carrying the COMT val/val genotype exhibited lower accuracy of sustained attention, associated with a more strict response bias, than val/val non-users. Cannabis users carrying the COMT val allele also committed more monitoring/shifting errors than cannabis users carrying the met/met genotype. Finally, cannabis users carrying the 5-HTTLPR s/s genotype had worse IGT performance than s/s non-users. COMT and SLC6A4 genes moderate the impact of cannabis use on executive functions.
大麻使用对执行功能的不良影响仍存在争议，这促使人们需要寻找新的生物标志物来揭示大麻消费对认知影响的个体差异。两种常见的遗传多态性与 Δ9-四氢大麻酚（THC）暴露的神经适应性影响以及动物的执行功能有关：儿茶酚-O-甲基转移酶（COMT）基因 val158met 多态性和 SLC6A4 基因 5-HTTLPR 多态性。我们旨在测试这些多态性是否调节年轻大麻使用者中大麻使用对执行功能的有害影响。我们招募了 144 名参与者：86 名大麻使用者和 58 名非药物使用者对照。两组均进行基因分型，并根据遗传背景、性别、年龄、教育程度和智商进行匹配。我们使用计算机化神经心理学测试来评估执行功能的不同方面：持续性注意力（CANTAB 快速视觉信息处理测试，RVIP）、工作记忆（N-back）、监测/转换（CANTAB ID/ED 转换）、计划（CANTAB 剑桥套索，SOC）和决策（爱荷华赌博任务，IGT）。我们使用基于一般线性模型的分析来测试大麻使用者和对照组之间作为基因型函数的表现差异。我们发现：（i）每日大麻使用与执行功能缺陷无关；（ii）COMT val158met 和 5-HTTLPR 多态性调节大麻使用与执行表现之间的联系。携带 COMT val/val 基因型的大麻使用者表现出较低的持续性注意力准确性，与更严格的反应偏差相关，而 val/val 非使用者则没有。携带 COMT val 等位基因的大麻使用者比携带 met/met 基因型的大麻使用者犯的监测/转换错误更多。最后，携带 5-HTTLPR s/s 基因型的大麻使用者的 IGT 表现比 s/s 非使用者差。COMT 和 SLC6A4 基因调节大麻使用对执行功能的影响。
